The quantification of chemical and biochemical components in aqueous fluids, and particularly in biological fluids such as whole blood or urine and in biological fluid derivatives such as serum and plasma, is of ever increasing importance. Important applications exist in medical diagnosis and treatment and in the quantification of exposure to therapeutic drugs, intoxicants, hazardous chemicals and the like. These applications include the detection and quantification of an increasing variety of certain circulating antibodies, cancer-related metabolites, genetically derived chemical tracers, and hormones emitted during events such as pregnancy. In many instances, the amounts of materials being determined are minuscule--in the range of a microgram or less per deciliter--and readily analyzed only by means of complicated apparatus operated by skilled laboratory personnel. In such cases the results are generally not available for some hours or days after sampling. In other instances, there is often an emphasis on the ability of lay operators to perform analytical tests routinely, quickly and reproducibly in a nonlaboratory setting, with rapid or immediate information display.
One common medical test is the measurement of blood glucose levels by diabetics. Current teaching counsels diabetic patients to measure their blood glucose level from two to seven times a day, depending on the nature and severity of their individual cases. Based on the observed pattern in the measured blood glucose levels, the patient and physician together make adjustments in diet, exercise and insulin intake to better manage the disease. Clearly, this information should be available to the patient at the time of sampling.
This glucose determination typically entails the diabetic piercing the skin of his or her finger with a lance, followed by squeezing or expression of a blood droplet. The blood droplet is then transferred to a reagent pad or test strip. The amount of blood that is conveniently expressed from a finger prick is governed by the size and depth of penetration of the lance. Too small a nick results in an inadequately sized blood sample for the intended analysis. Pain is experienced in the lancing procedure, and the degree of pain is associated with the size and depth of penetration of the lance. Unfortunately, with current technology, a lancet size and required depth of penetration entails significant pain. The continual daily lancing of one's fingertips is a painful exercise necessarily tolerated by diabetics once or twice per day. More frequent testing than this, however, would bring on a serious problem of patient noncompliance, if required.
If the blood droplet size needed for a blood glucose determination can be significantly reduced, the pain associated with finger pricking can also be greatly reduced by reason of use of smaller lances and/or decreased depth of penetration into the flesh of the finger. There is indeed a need for an analytical sampling method, suitable for use by a diabetic patient, that requires less blood than current devices and methods, and which is therefore associated with less pain.
Determination of analytes in whole blood often involves colorimetric determinations utilizing color-generating reagents immobilized within reagent pads or porous media. The presence of red blood cells or other colored components in blood often interferes with such measurements. Exclusion of red blood cells and/or other blood cellular components has been practiced utilizing reagent pads with filterative or membranous layers specifically formed or laminated thereon. This tends to increase the complexity of such devices, as well as increasing the volume of blood that must be applied. Accordingly, in addition to the need for a smaller blood sample, a need also exists for a means of excluding cellular components of blood and body fluids without increasing the fluid sample size.
It is an object of this invention to provide a minimally invasive means of detecting and measuring analytes in both whole blood and other biological fluids. With regard to whole blood, it is a further object of this invention to provide a device capable of detecting and/or quantifying analytes without requiring a prior removal step for cellular blood components before blood contact with the device.
Another object of this invention to provide a device capable of detecting and/or quantifying a multiplicity of analytes in a single droplet of a bodily fluid.
Another object of this invention to provide a diabetic patient with a means of analyzing blood glucose concentrations in a manner that significantly reduces the pain associated with providing a sufficient blood sample for the glucose analysis.
These and other objects of the invention will be apparent to those skilled in this art from the following detailed description of preferred embodiments of the invention.